Celiac disease (CD) is the most common food sensitive enteropathy known, affecting approximately 1% of the population and its incidence appears to be on the rise. In addition, non-celiac gluten sensitivity (GS) has recently been revealed to be a distinct condition that affects a growing number of individuals. Both of these conditions are triggered by gluten, a complex mixture of proline and glutamine-rich seed storage proteins found in wheat, barley and rye. Because these proteins are resistant to digestion they persist in the gastrointestinal tract and cause an auto-inflammatory response in susceptible individuals. Currently the only treatment for these conditions is the maintenance of a strict glute free diet. This proposal will test the safety of reduced gluten (RG) cereal grains, using barley a a model cereal, in combination with a gluten degrading enzyme supplement in a non-human primate model of celiac disease, the rhesus macaque. Rhesus macaques have been shown to develop a condition that is analogous to human celiac disease when gluten is included in their diet, and the condition improves upon gluten withdrawal. In ongoing research, the PI has been identifying low gluten variants of barley and wheat, while the academic collaborators have been developing the animal model of celiac disease, and a gluten-degrading protease supplement, respectively. Eliminating all gluten from the diet can be difficult for those suffering from CD or GS, and the use of a gluten degrading supplement by itself is not intended to permit these groups to resume unrestricted gluten consumption. We believe that a synergistic therapy combining reduced gluten grains with a gluten protease supplement may provide the opportunity for these individuals to introduce limited quantities of reduced gluten cereals into their diets. Testing this hypothesis in a non-human primate model is the objective of the proposed research. The commercial outcome of this proposal will be reduced gluten variants of barley for which there will be increased assurance of acceptability for multiple food products. RG barley represents a new category of cereal grain that may play a role in providing an alternative to the gluten free diet for CD and GS individuals in combination with other therapies. The wide adoption of RG barley and other RG grains could ultimately reduce the incidence of these conditions. Basic knowledge about the seed characteristics of RG barley may pave the way for RG wheat.